Cerebellar lesions at a young age predict poorer long-term functional recovery

Abstract

Early studies on long-term functional recovery after motor and premotor lesions showed better outcomes in younger monkeys than in older monkeys. This finding led to the widespread belief that brain injuries cause less impairment in children than adults. However, this view has limitations and a large body of evidence now indicates that cerebral damages can be more harmful when inflicted at young age, during critical periods of neural development. To date, this issue has been mainly investigated in the context of focal and diffuse cortical lesions. Much less is known about the potential influence of early cerebellar damages. Several studies exist in survivor of posterior fossa tumours. However, in these studies, critical confounders were not always considered and contradictory conclusions were provided. We studied the impact or early cerebellar damage on long-term functional recovery in three groups of 15 posterior fossa survivors, comparable with respect to their tumour characteristics (type, size and location) but operated at different ages: young (≤7 years), middle (>7 and ≤13 years) and older (>13 years). Daily (health-related quality of life scale, performance status scale), motor (International Cooperative Ataxia Rating Scale, Pegboard Purdue Test) and cognitive (full-scale intelligence quotient) functioning were assessed. A general linear model controlling for age at surgery, radiotherapy, preservation of deep cerebellar nuclei, tumour volume and delay between surgery and assessment was used to investigate significant variations in outcome measures. Early age at surgery, lesion of deep cerebellar nuclei and postoperative radiotherapy had a significant, independent negative influence on long-term recovery. Tumour volume and delay between surgery and assessment had no statistically detectable impact. The negative influence of early age at surgery was significant in all domains: daily functioning (health-related quality of life scale, performance status scale), motor functioning (International Cooperative Ataxia Rating Scale, Pegboard Purdue Test) and cognitive functioning (full-scale intelligence quotient). These results support the existence of an early critical period of development during which the cerebellar ‘learning machine’ is of critical importance. Although the extent to which the early deficits here observed can be reversed needs now to be established, our data plead for the implementation of prompt and intense rehabilitation interventions in children operated before 7 years of age.

A New Insight on the Role of the Cerebellum for Executive Functions and Emotion Processing in Adults

“…Some studies reported that cerebellar damage at a young age contributed to more severe, and prolonged impairment in both cognitive and motor domains ( 41 , 42 ). However, multiple caveats in experimental design limited those studies ( 43 ). Beuriat et al, in a study of patients who were treated for a posterior fossa tumor, controlled all the major confounders (namely radiotherapy, tumor characteristics, damage to the deep cerebellar nuclei, and delay between surgery and assessment time) and reported that younger children had worse long-term performance compared to older children or adults in motor and cognitive tasks ( 43 ).…”

“…However, multiple caveats in experimental design limited those studies ( 43 ). Beuriat et al, in a study of patients who were treated for a posterior fossa tumor, controlled all the major confounders (namely radiotherapy, tumor characteristics, damage to the deep cerebellar nuclei, and delay between surgery and assessment time) and reported that younger children had worse long-term performance compared to older children or adults in motor and cognitive tasks ( 43 ). Since our participants suffered their injury at an adult age, it might also be a key factor that explains our lack of significant findings in our sub-group of cerebellar participants.…”

The shifting role of the cerebellum in executive, emotional and social processing across the lifespan

“…Only, Aarsen et al described a negative effect [ 1 ]. However, multiple caveats limited those studies [ 6 ]. Beuriat et al in a study of patients who were treated for a posterior fossa tumor, controlled all the major confounders (namely radiotherapy, tumor characteristics, damages to the deep cerebellar nuclei and delay between surgery and assessment time) and reported that early cerebellar damage (≤ 7 years old) is an independent factor for poor long-term functional (cognitive and motor) outcome [ 6 ].This suggests that the cerebellum is a sort of “broad learning machine”, and that during critical periods of development, the cerebellum, as part of a distributed neural network, is the foundation for future motor and cognitive learning.…”

“…Clinical studies reporting the outcome of patients with acute cerebellar injury or chronic neurodegeneration have shown that the degree of cognitive impairment and the long-term effect of the injury is worse in younger children [ 1 , 6 ]. Preterm cerebellar injuries are also associated with poor motor and cognitive outcome [ 59 ].…”

Preoperative 11C-Methionine PET-MRI in Pediatric Infratentorial Tumors

“…Although symptomatic posterior fossa tumors are typically resected, it has been reported that posterior fossa surgery may have a critical impact on the sensorimotor and cognitive outcomes of children. 14,15 The current management of brain tumors in children is evolving due to an improved understanding of the molecular mechanisms, even though biomarkers are lacking. The complementary information provided by PET and MRI, for example, SUV and ADC, could improve tumor characterization and, indirectly, the use of molecular targeted therapies.…”